Trasiocation affects normalc-mycpromoter usage and activates fifteen crypticc-myctranscription starts in plasmacytoma M603

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Abstract
Plasmacytoma M603 contains one normal, nontranslocated c- myc gene and one translocated c- myc gene 1n which c- myc exon l is juxtaposed with the immunoglobulin heavy chain enhancer and c- myc exons 2 and 3 are juxtaposed with Ca. We find that steady-state c- myc RNA levels are 2–4 fold elevated in M603 relative to normal liver or spleen and that these transcripts originate predominantly if not exclusively from the translocated c- myc gene. Although both promoters on the nontranslocated c- myc gene are repressed, the proximal promoter, Pl, is active on the translocated 5′ c- myc region which is juxtaposed with the immunoglobulin heavy chain enhancer. The 3′ portion of the translocated c- myc gene is transcribed from fifteen cryptic start sites and spliced at aberrant donor and acceptor splice sites, thereby generating a mixture of transcripts with different, abnormal 5′ untranslated regions. Although the reason that translocation activates the cryptic c- myc starts in M603 is not completely understood, we show that truncation of the c- myc gene is not sufficient to activate cryptic transcription sites.